COVID-19 and market structure dynamics.

We examine the impact of COVID-19 on market structure in the U.S. Specifically, we analyze the impact of both the COVID-19-induced market uncertainty period as well as the suspension of the NYSE floor on trading dynamics such as market fragmentation, algorithmic trading, and hidden liquidity in the market. During both the heightened market uncertainty and NYSE floor suspension periods, we find a significant increase in hidden liquidity yet significant decreases in both algorithmic trading and market fragmentation. However, despite withdrawing from the market during this period, remaining algorithmic traders appear to improve market quality. Our results indicate that COVID-19 had a significant impact on order routing, pre-trade transparency, and automated trading.

T-bet+ B cells Dominate the Peritoneal Cavity B Cell Response during Murine Intracellular Bacterial Infection.

T-bet+ B cells have emerged as a major B cell subset associated with both protective immunity and immunopathogenesis. T-bet is a transcription factor associated with the type I adaptive immune response to intracellular pathogens, driving an effector program characterized by the production of IFN-γ. Murine infection with the intracellular bacterium, Ehrlichia muris, generates protective extrafollicular T cell-independent T-bet+ IgM-secreting plasmablasts, as well as T-bet+ IgM memory cells. Although T-bet is a signature transcription factor for this subset, it is dispensable for splenic CD11c+ memory B cell development, but not for class switching to IgG2c. In addition to the T-bet+ plasmablasts found in the spleen, we show that Ab-secreting cells can also be found within the mouse peritoneal cavity; these cells, as well as their CD138- counterparts, also expressed T-bet. A large fraction of the T-bet+ peritoneal B cells detected during early infection were highly proliferative and expressed CXCR3 and CD11b, but, unlike in the spleen, they did not express CD11c. T-bet+ CD11b+ memory B cells were the dominant B cell population in the peritoneal cavity at 30 d postinfection, and although they expressed high levels of T-bet, they did not require B cell-intrinsic T-bet expression for their generation. Our data uncover a niche for T-bet+ B cells within the peritoneal cavity during intracellular bacterial infection, and they identify this site as a reservoir for T-bet+ B cell memory.

Adenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity.

CD11c+T-bet+ B cells are recognized as an important component of humoral immunity and autoimmunity. These cells can be distinguished from other B cells by their higher expression of the adenosine receptor 2a. Here we address whether A2A receptor activation can affect CD11c+T-bet+ B cells. We show that administration of the A2A receptor agonist CGS-21680 depletes established CD11c+T-bet+ B cells in ehrlichial-infected mice, in a B cell-intrinsic manner. Agonist treatment similarly depletes CD11c+T-bet+ B cells and CD138+ B cells and reduces anti-nuclear antibodies in lupus-prone mice. Agonist treatment is also associated with reduced kidney pathology and lymphadenopathy. Moreover, A2A receptor stimulation depletes pathogenic lymphocytes and ameliorates disease even after disease onset, highlighting the therapeutic potential of this treatment. This study suggests that targeting the adenosine signaling pathway may provide a method for the treatment of lupus and other autoimmune diseases mediated by T-bet+ B cells.

Transaxillary Stenting of LVAD Outflow Graft Obstruction.

An 82-year-old man with a HeartMate II left ventricular assist device presented with low-flow alarms and cardiogenic shock secondary to left ventricular assist device outflow graft obstruction. Given high risk for redo sternotomy, the heart team decided on percutaneous intervention with peripheral stents, a procedure that is currently limited to case reports. (Level of Difficulty: Advanced.).

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.

Genotypic and Phenotypic Characterization of Incompatibility Group FIB Positive Salmonella enterica Serovar Typhimurium Isolates from Food Animal Sources.

Salmonella enterica is one of the most common bacterial foodborne pathogens in the United States, causing illnesses that range from self-limiting gastroenteritis to more severe, life threatening invasive disease. Many Salmonella strains contain plasmids that carry virulence, antimicrobial resistance, and/or transfer genes which allow them to adapt to diverse environments, and these can include incompatibility group (Inc) FIB plasmids. This study was undertaken to evaluate the genomic and phenotypic characteristics of IncFIB-positive Salmonella enterica serovar Typhimurium isolates from food animal sources, to identify their plasmid content, assess antimicrobial resistance and virulence properties, and compare their genotypic isolates with more recently isolated S. Typhimurium isolates from food animal sources. Methods: We identified 71 S. Typhimurium isolates that carried IncFIB plasmids. These isolates were subjected to whole genome sequencing and evaluated for bacteriocin production, antimicrobial susceptibility, the ability to transfer resistance plasmids, and a subset was evaluated for their ability to invade and persist in intestinal human epithelial cells. Results: Approximately 30% of isolates (n = 21) displayed bacteriocin inhibition of Escherichia coli strain J53. Bioinformatic analyses using PlasmidFinder software confirmed that all isolates contained IncFIB plasmids along with multiple other plasmid replicon types. Comparative analyses showed that all strains carried multiple antimicrobial resistance genes and virulence factors including iron acquisition genes, such as iucABCD (75%), iutA (94%), sitABCD (76%) and sitAB (100%). In 17 cases (71%), IncFIB plasmids, along with other plasmid replicon types, were able to conjugally transfer antimicrobial resistance and virulence genes to the susceptible recipient strain. For ten strains, persistence cell counts (27%) were noted to be significantly higher than invasion bacterial cell counts. When the genome sequences of the study isolates collected from 1998-2003 were compared to those published from subsequent years (2005-2018), overlapping genotypes were found, indicating the perseverance of IncFIB positive strains in food animal populations. This study confirms that IncFIB plasmids can play a potential role in disseminating antimicrobial resistance and virulence genes amongst bacteria from several food animal species.

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD). IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over time. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells play an important role in SARS-CoV-2 immunity.

Avoidance behavior independent of innate-immune signaling seen in Caenorhabditis elegans challenged with Bacillus anthracis.

Small organisms, like the nematode C. elegans, are emerging as insightful models in which to study host/pathogen interactions and the evolving interplay between host defenses and microbial offenses. In C. elegans the innate immune response has been shown to be connected to the DAF-2 insulin/insulin-like growth factor 1 (IGF-1) signal pathway, a critical transduction pathway that mediates stress response in the worms via the DAF-16 FOXO/forkhead transcription factor. Our studies of the C. elegans' phenotypes that are associated with behavioral innate immune response (avoidance behavior) and IGF-1 signaling perturbations (lifespan effects) led us to question the cause of the avoidance behavior observed when C. elegans are challenged with B. anthracis. While worms indeed avoid B. anthracis, and this behavior seems to be partly tied to IGF-1 signaling, the bacteria have neither nematocidal nor visible pathogenic effects on the worms. In fact, worms fed B. anthracis alone exhibit extended lifespans. We demonstrate that the extended lifespan phenotype seen in worms fed B. anthracis is likely the result of calorie restriction, and that worms do not eat B. anthracis even when avoidance behaviors have been suppressed. We further demonstrate a large time lag between the onset of avoidance behavior (which occurs upon contact with B. anthracis), and the induction of IGF-1 signaling (which occurs much later) in worms fed B. anthracis. Taken together, our data demonstrate behavioral avoidance that does not appear to be linked to a measurable immune response. We propose that, in some situations, avoidance behaviors categorized as immunological might be more accurately described as broad foraging behaviors induced in worms presented with a non-preferred food choice, or with a food choice that is either difficult or impossible for the worms to ingest.

When the pressure drops: A case of vasoplegia during a structural heart intervention.

A 67-year-old male underwent general anesthesia for left atrial appendage occlusion. During the procedure, the patient developed catecholamine refractory hypotension requiring the administration of several vasopressin boluses to maintain adequate perfusion pressure. At the conclusion of the procedure, mild venous bleeding necessitated the administration of protamine. This led to a further decrease in the patient's blood pressure. Tamponade and continued volume loss were quickly ruled out leading to a diagnosis of vasoplegia syndrome (VS). The patient was appropriately treated with a vasopressin infusion with normalization of blood pressure and no significant morbidity or adverse outcome. With the use of general anesthesia during structural heart interventions on the rapid rise, we discuss the two common causes for vasoplegia along with evidence-based treatments and possible prevention strategies.

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

High-pressure post-dilation following transcatheter valve-in-valve implantation in small surgical valves.

AIMS: Residual gradients >20 mmHg after transcatheter valve-in-valve (ViV) implantation are associated with worse survival. This study aimed to evaluate the feasibility of high-pressure post-dilation with a non-compliant balloon after transcatheter ViV implantation in small surgical valves to optimise haemodynamics. METHODS AND RESULTS: Thirty patients underwent ViV implantation in surgical valves with internal dimension ≤19 mm. High-pressure post-dilation to 16-20 atmospheres with a non-compliant balloon was performed in 12 patients and 18 patients underwent ViV without post-dilation. SAPIEN 3 and Evolut valves were used in 10 and two patients, respectively. The mean aortic valve (AV) gradient decreased by 11.3 mmHg following high-pressure post-dilation (18.7±7.9 mmHg immediately post ViV to 7.5±2.6 mmHg following high-pressure post-dilation, p<0.01). There were no cases of aortic root rupture. High-pressure post-dilation, compared to no post-dilation, was associated with lower invasive AV mean gradients at the end of the ViV procedure (8.2±3.5 mmHg vs. 17.3±7.9 mmHg, p=0.001) as well as lower day 1 (18.0±4.5 mmHg vs. 25.0±8.1 mmHg, p=0.016) and 30-day gradients (19.8±2.5 vs. 26.5±11.0, p=0.038) on transthoracic echocardiography. CONCLUSIONS: High-pressure post-dilation of small surgical valves following transcatheter ViV implantation results in a significant improvement in post-procedure haemodynamics.

Optical coherence tomography guided carotid artery stent procedure: technique and potential applications.

OBJECTIVES: To (1) present a guide on how to perform optical coherence tomography (OCT) in carotid artery stenting (CAS), to (2) highlight several instructive cases illustrating OCT-guidance as an interventional strategy, and to (3) present the largest case-series of OCT-guided CAS performed in North America, demonstrating its feasibility as an imaging modality in this setting. BACKGROUND: OCT is an intravascular imaging method that captures images with an axial resolution 10 times higher than intravascular ultrasound. OCT has proven to be a useful modality in coronary angiography and may have similar applications in evaluating carotid atherosclerotic disease. METHODS: We compared our experience in CAS utilizing OCT (40 patients) versus that of CAS without OCT guidance (52 patients). RESULTS: No strokes or deaths occurred in either group postprocedurally or at 12 months. Fluoroscopy time was reduced in the OCT arm (14 ± 1 vs. 16 ± 1 min). Postprocedural creatinine levels were identical (1 ± 0 mg/dl, P = 0.96). Procedure time (96 ± 8 vs. 80 ± 3 min, P = 0.06) and contrast use (94 ± 4 vs. 83 ± 4 ml, P = 0.05) was slightly elevated in the OCT arm. CONCLUSIONS: We established a standardized protocol to consistently obtain OCT images that helped guide interventional decision-making during CAS. OCT imaging in the carotids requires a higher contrast load and prolongs procedure time. However, it can be performed without significant increases in fluoroscopy time or negatively affecting renal function. There were no negative safety signals in this pilot study.

Development and Early Experience of the First Joint Military Health System-Veterans Affairs Transcatheter Aortic Valve Replacement Program.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a minimally invasive cardiac surgical procedure that has revolutionized the treatment of aortic stenosis. This is the most common valvular heart condition in developed countries, affecting 3.4% of those ages 75 and above. Because there is no medical therapy that can arrest progression of the disease, valve replacement forms the cornerstone of therapy. METHODS: Naval Medical Center San Diego and the VA San Diego Healthcare System have developed a unique collaborative TAVR program-a first in the Department of Defense-to offer this revolutionary procedure to their beneficiaries. Herein, we review development of the program and outcome for patients referred during the first 9 months. FINDINGS: Development of the program was a multiyear process made successful because of administrative support, facility upgrades, and collaboration within the crossfacility and multispecialty heart valve team. In the first 9 months, 29 patients were referred for evaluation. Twenty-two (average age 80 years) underwent TAVR, whereas others were deemed nonoperable or were pending disposition at the time of this report. Patients who underwent TAVR had a predicted risk of procedural mortality from surgical aortic valve replacement of 7.7%, similar to other trials and registry studies. After mean follow-up of 5.6 months (range 30-355 days), zero deaths were recorded in the patients who underwent TAVR. Compared to other nonfederal local institutions, the program also realized a cost savings of approximately 17%, or nearly $10,000, per patient. DISCUSSION: In the first 9 months, results were positive and consistent with expectations from national and international registries. Our hope is that this program may serve as an example for other federal facilities looking to start their own combined programs to improve health care quality and patient experience while simultaneously achieving considerable cost containment within a constrained national health care budget.

Transcatheter Procedure for Residual Mitral Regurgitation After MitraClip Implantation Using Amplatzer Duct Occluder II.

OBJECTIVES: This study reports a novel transcatheter procedure for residual mitral regurgitation (MR) after MitraClip implantation using the Amplatzer Duct Occluder II (ADO II). BACKGROUND: Although the MitraClip procedure is a transcatheter treatment option for patients at high surgical risk with severe MR, management of significant residual MR after MitraClip implantation is still challenging. METHODS: We describe a case series of 9 consecutive patients who underwent transcatheter deployment of the ADO II plug for significant residual MR after MitraClip implantation from April to October 2015. RESULTS: The mean age was 79.3 ± 11.4 years. The deployment of the ADO II plug was performed at the initial MitraClip procedure in 7 patients and at the second procedure for recurrent symptoms in 2 patients. There were 2 types of residual MR seen after MitraClip implantation: residual commissural MR (n = 3) and residual intraclip MR (n = 6). The ADO II was successfully deployed with significant reduction of MR flow and left atrial pressure in all patients. The ADO II plug was retrieved in 1 patient because of device embolization to the ostial right coronary artery. However, all patients were discharged 1.8 ± 1.2 days after the procedure, with no significant MR on pre-discharge transthoracic echocardiography. In 8 patients who underwent 1-month symptomatic assessment, clinical symptoms were diminished to New York Heart Association functional class I or II. CONCLUSIONS: Transcatheter deployment of the ADO II plug was effective for the reduction of residual commissural MR and intraclip MR after MitraClip implantation. The potential role of this technique should be established for challenging cases.

Don't you forget about me! The 80s still matter!

Invasive therapy had a significantly lower odds ratio of death at 28 days in elderly patients. Patients treated with a conservative approach received significantly less guideline directed medical therapy. The highest risk (those most likely to benefit) were less likely to get invasive therapy.

Impact of body mass index on the outcomes following transcatheter aortic valve implantation.

OBJECTIVES: To investigate the influence of body mass index (BMI) on short- and midterm outcomes following transcatheter aortic valve implantation (TAVI). BACKGROUND: Although obesity is a major risk factor for cardiovascular mortality, numerous studies reported a beneficial effect of obesity on survival in patients with cardiovascular disease and in patients after cardiac interventions. Moreover, all previous reports examining the relation between BMI and outcomes following TAVI have underscored the "obesity paradox" in these patients. METHODS: During a 3 year period, 805 patients with severe aortic stenosis that underwent TAVI at our institute were evaluated. Based on baseline BMI, patients were classified as normal weight (18.5-24.9 kg/m(2) ), overweight (25.0-29.9 kg/m(2) ), or obese (≥30 kg/m(2) ). TAVI endpoints, device success, and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions. RESULTS: Obese patients were significantly younger, had higher prevalence of diabetes mellitus and chronic lung disease, and had lower prevalence of frailty. Device success was similar between the 3 groups. All-cause mortality up to 30 days was 2.9% (10/340) vs 4.5% (12/268) vs 0.5% (1/186) in patients with normal weight, overweight, and obesity, respectively (p = 0.048). In a multivariable model, overweight and obese patients had similar overall mortality compared to patients with normal weight. CONCLUSIONS: We found no evidence for the existence of an obesity paradox following TAVI. Correction for possible confounders such as frailty in the present cohort may explain the discrepancy between the current report and the previous reports that suggested a protective effect for increased BMI following TAVI. © 2016 Wiley Periodicals, Inc.

Impact of Preprocedural B-Type Natriuretic Peptide Levels on the Outcomes After Transcatheter Aortic Valve Implantation.

There are limited data on the effect of baseline B-type natriuretic peptide (BNP) on the outcome after transcatheter aortic valve implantation (TAVI). We investigated the influence of baseline BNP levels on the short-term and midterm clinical outcomes after TAVI. During a 3-year period, 780 patients with severe aortic stenosis underwent TAVI at our institute and had baseline BNP levels. We compared the high, mid, and low tertiles of BNP levels. TAVI end points, device success, and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Device success was significantly lower for patients with high BNP (98.1% vs 96.2% vs 91.9% for the low, mid, and high BNP tertiles, respectively; p = 0.003). All-cause mortality up to 30 days was 1.2% (3 of 260) versus 2.3% (6 of 260) versus 5% (13 of 260), respectively (p = 0.03). Six-month mortality rate was 4.1% (10 of 241) for the low BNP tertile, 5% (12 of 239) for the mid BNP tertile, and 17.1% (40 of 234) for the high BNP tertile (p <0.001). In the multivariate model, high tertile of baseline BNP was found to be significantly associated with all-cause mortality (hazard ratio 3.3, 95% confidence interval 1.64 to 6.48; p = 0.001). In conclusion, elevated BNP levels are associated with increased short-term and midterm mortality after TAVI. We recommend measurement of baseline BNP as part of risk stratification models for TAVI.

An adult with a sinus venosus atrial septal defect and dilated cardiomyopathy.

Dilated cardiomyopathy, heart failure and atrial septal defects are well-recognised entities in isolation, but are rarely seen together. Now that 90% of children with congenital heart disease survive into adulthood, such combinations of disease are increasingly seen in adult cardiology. While most young patients with dilated cardiomyopathy respond well to medical therapy, some do not, and require more invasive management. We describe a 32 year-old man with dilated cardiomyopathy and a sinus venosus-type atrial septal defect associated with a remarkable pulmonary to systemic flow ratio of 5:1. We propose that the atrial septal defect blunted his heart failure symptoms by serving as a 'pop-off' valve and limiting pulmonary congestion. The patient ultimately failed medical management and received a left ventricular assist device. The case is presented along with a discussion of this unique pathophysiology and a brief review of the literature in this rapidly evolving field.